Long-term care (LTC) patients are often sent to emergency departments (EDs) by ambulance. In this novel extended care paramedic (ECP) program, specially trained paramedics manage LTC patients on ...site. The objective of this pilot study was to describe the dispatch and disposition of LTC patients treated by ECPs and emergency paramedics.
Data were collected from consecutive calls to 15 participating LTC facilities for 3 months. Dispatch determinants, transport rates, and relapse rates were described for LTC patients attended by ECPs or emergency paramedics. ECP involvement in end-of-life care was identified.
Of 238 eligible calls, 140 (59%) were attended by an ECP and 98 (41%) by emergency paramedics. Although the top three determinants were the same in each group, the overall distribution of dispatch determinants and acuity differed. In the ECP cohort, 98 of 140 (70%) were treated and released, 33 of 140 (24%) had "facilitated transfer" arranged by an ECP, and 9 of 140 (6%) were immediately transported to the ED by ambulance. In the emergency paramedic cohort, 77 of 98 (79%) were immediately transported to the ED and 21 of 98 (21%) were not transported. In the ECP group, 6 of 98 (6%) patients not transported triggered a 911 call within 48 hours for a related clinical reason, although none of the patients not transported by emergency paramedics relapsed.
ECP involvement in LTC calls was found to reduce transports to the ED with a low rate of relapse. These pilot data generated hypotheses for future study, including determination of appropriate populations for ECP care and analysis of appropriate and safe nontransport.
Emergency medical services (EMS) programs, which provide an alternative to traditional EMS dispatch or transport to the emergency department (ED), are becoming widely implemented. This scoping review ...identified and catalogued all outcomes used to measure such alternative EMS programs. Data Source Broad systematized bibliographic and grey literature searches were conducted. Study Selection Inclusion criteria were 911 callers/EMS patients, reported on alternatives to traditional EMS dispatch OR traditional EMS transport to the ED, and reported an outcome measure. Data Extraction The reports were categorized as either alternative to dispatch or to EMS transport, and outcome measures were categorized and described. Data Synthesis The bibliographic search retrieved 13,215 records, of which 34 articles met the inclusion criteria, with an additional 10 added from reference list hand-searching (n=44 included). In the grey literature search, 31 websites were identified, from which four met criteria and were retrieved (n=4 included). Fifteen reports (16 studies) described alternatives to EMS dispatch, and 33 reports described alternatives to EMS transport. The most common outcomes reported in the alternatives to EMS dispatch reports were service utilization and decision accuracy. Twenty-four different specific outcomes were reported. The most common outcomes reported in the alternatives to EMS transport reports were service utilization and safety, and 50 different specific outcomes were reported.
Numerous outcome measures were identified in reports of alternative EMS programs, which were catalogued and described. Researchers and program leaders should achieve consensus on uniform outcome measures, to allow benchmarking and improve comparison across programs.
Research is essential for the development of evidence-based emergency medical services (EMS) systems of care. When resources are scarce and gaps in evidence are large, a national agenda may inform ...the growth of EMS research in Canada. This mixed methods consensus study explores current barriers and existing strengths within Canadian EMS research, provides recommendations, and suggests EMS topics for future study.
Purposeful sampling was employed to invite EMS research stakeholders from various roles across the country. Study phases consisted of 1) baseline interviews of a subsample, 2) roundtable discussion, and 3) an online Delphi survey, in which participants scored each statement for importance. Consensus was defined a priori and met if 80% scored a statement as "important" or "very important."
Fifty-three stakeholders participated, representing researchers (37.7%), EMS administrators (24.6%), clinicians/providers (20.7%), and educators (17.0%). Participation rates were as follows: interviews, 13 of 13 (100%); roundtable, 47 of 53 (89%); survey round 1, 50 of 53 (94%); survey round 2, 47 of 53 (89%); and survey round 3, 40 of 53 (75%). A total of 141 statements were identified as important: 20 barriers, 54 strengths/opportunities, 31 recommendations, and 36 suggested topics for future research. Like statements were synthesized, resulting in barriers (n = 10), strengths/opportunities (n = 24), and recommendations (n = 19), which were categorized as time, opportunities, and funding; education and mentorship; culture of research and collaboration; structure, process, and outcome of research; EMS and paramedic practice; and the future of the EMS Research Agenda.
Consensus-based key messages from this agenda should be considered when designing, funding, and publishing EMS research and will advance EMS research locally, regionally, and nationally.
Objectives: The principles of evidence‐based medicine are applicable to all areas and professionals in health care. The care provided by paramedics in the prehospital setting is no exception. The ...Prehospital Evidence‐based Protocols Project Online (PEP) is a repository of appraised research evidence that is applicable to interventions performed in the prehospital setting and is openly available online. This article describes the history, current status, and potential future of the project.
Methods: The primary objective of the PEP is to catalog and grade emergency medical services (EMS) studies with a level of evidence (LOE). Subsequently, each prehospital intervention is assigned a class of recommendation (COR) based on all the appraised articles on that intervention, in an effort to organize the evidence so it may be put into practice efficiently. An LOE is assigned to each article by the section editor, based on the study rigor and applicability to EMS. The section editor committee consists of EMS physicians and paramedics from across Canada, and two from Ireland and a paramedic coordinator. The evidence evaluation cycle is continuous; as the section editors send back appraisals, the coordinator updates the database and sends out another article for review.
Results: The database currently has 182 individual interventions organized under 103 protocols, with 933 citations.
Conclusions: This project directly meets recent recommendations to improve EMS by using evidence to support interventions and incorporating it into protocols. Organizing and grading the evidence allows medical directors and paramedics to incorporate research findings into their daily practice. As such, this project demonstrates how knowledge translation can be conducted in EMS.
Many health care disciplines use evidence-based decision making to improve patient care and system performance. While the amount and quality of emergency medical services (EMS) research in Canada has ...increased over the past two decades, there has not been a unified national plan to enable research, ensure efficient use of research resources, guide funding decisions and build capacity in EMS research. Other countries have used research agendas to identify barriers and opportunities in EMS research and define national research priorities. The objective of this project is to develop a national EMS research agenda for Canada that will: 1) explore what barriers to EMS research currently exist, 2) identify current strengths and opportunities that may be of benefit to advancing EMS research, 3) make recommendations to overcome barriers and capitalize on opportunities, and 4) identify national EMS research priorities.
Paramedics, educators, EMS managers, medical directors, researchers and other key stakeholders from across Canada will be purposefully recruited to participate in this mixed methods study, which consists of three phases: 1) qualitative interviews with a selection of the study participants, who will be asked about their experience and opinions about the four study objectives, 2) a facilitated roundtable discussion, in which all participants will explore and discuss the study objectives, and 3) an online Delphi consensus survey, in which all participants will be asked to score the importance of each topic discovered during the interviews and roundtable as they relate to the study objectives. Results will be analyzed to determine the level of consensus achieved for each topic.
A mixed methods approach will be used to address the four study objectives. We anticipate that the keys to success will be: 1) ensuring a representative sample of EMS stakeholders, 2) fostering an open and collaborative roundtable discussion, and 3) adhering to a predefined approach to measure consensus on each topic. Steps have been taken in the methodology to address each of these a priori concerns.
Background: Recent data suggests that older patients with acute myeloid leukemia (AML) have a higher frequency of poor risk TP53 mutations (TP53mut) than previously suspected. Patients with TP53mut ...have a very poor prognosis, making this AML sub-group an area of high unmet therapeutic need. Although recent clinical trials suggest promising response rates for the BCL-2 inhibitor venetoclax (Ven) in combination with DNA methyltransferase inhibitors (DNMTi) or low-dose cytarabine, survival outcomes remain poor among patients with TP53mut (Strickland et al, EHA 2018).
Methods and Results: To identify novel therapies effective against TP53mut AML, isogenic TP53 knockout cells (TP53 KO) were generated by CRISPR/Cas9 in OCI-AML3, MV4;11 and MOLM-13 human AML cell lines. In a drug screen of 50 compounds, we identified AZD2811, an aurora kinase B inhibitor, which potently killed AML cells independently of TP53 genotype (Figure 1). We hypothesised that AZD2811 would synergise with Ven to overcome venetoclax-resistance in TP53-mutant AML. Consistent with this, AZD2811 and venetoclax showed strong synergy (Loewe score <4) in 6 AML cell lines independent of TP53 genotype, and combined treatment displayed highly efficacious activity in both TP53 KO cells and wild type control cells in vitro (Figure 2). Immunoblot of treated cells revealed that AZD2811 depleted MCL-1 expression in the majority of cases, a known cause of venetoclax resistance. AZD2811 was also active in killing Bax/Bak knockout cells, suggesting that the mechanism of AZD2811 may not be limited to the intrinsic apoptosis pathway. Using a competitive growth assay incorporating a fluorescent reporter for TP53 KO cells, we showed the relative resistance of TP53 defective cells to Ven and decitabine (DEC) alone, as well as Ven + DEC, compared to wild type cells. In contrast, TP53 KO cells showed no competitive growth advantage when exposed to an initially sub-lethal dose of AZD2811 (10 nM), compared to TP53 WT cells. Interestingly, continuous exposure to AZD2811 resulted in a catastrophic collapse in cell viability on day 10, unlike comparator anti-leukemic agents (Figure 4). In vivo efficacy for nanoparticle formulated AZD2811 (NP) was observed in SCID mice xenografted with HL-60 cells (known to be TP53 mutant), where combined treatment of AZD2811NP and Ven significantly prolonged animal survival (Figure 3). Remarkably, combined AZD2811NP and Ven treatment was more effective than Ven + azacitidine treatment in vivo. Patient-derived xenograft (PDX) models to verify the activity of AZD2811NP + venetoclax against primary AML cases with TP53 mutations will be presented at the meeting.
Conclusions: We report for the first time that AZD2811NP can overcome venetoclax resistance in TP53-mutant AML in vitro and in vivo. These findings therefore, support the clinical investigation of combined aurora kinase and BCL-2 targeting in the clinic for patients with TP53-mutant AML, who currently lack effective treatment options.
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Urosevic:AstraZeneca: Employment. Polanska:AstraZeneca: Employment. Cosaert:AstraZeneca: Employment. Pease:AstraZeneca: Employment, Equity Ownership. Travers:AstraZeneca: Employment. Wei:Pfizer: Honoraria; Janssen: Honoraria; Walter and Eliza Hall Institute: Other: former employee, Patents & Royalties: receives a fraction of its royalty stream related to venetoclax; AbbVie: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Macrogenics: Honoraria; Astellas: former employee, Honoraria; Genentech: Honoraria; Servier: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; AstraZeneca: Honoraria, Research Funding.
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